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MT-RNR2 Gene
Overview The human MT-RNR2 gene, also known as mrRNA16S when referenced throughout the rest of eukaryotic taxa, is one of two mitochondrial genes encoding ribosomal RNA (rRNA). MTRNR2 is the biggest subunit of the two-mitochondrial rRNA strands, with the smaller one being MT-RNR1 (mrRNA12S gene). MT-RNR2 is also part of the genes responsible for encoding humanin polypeptide (HN); a neuro-protective factor associated with prevention of Alzheimer and cell-stress alleviation (Bodzioch, et al. 2009). The mrRNA 16S gene corresponds to Eukaryotic organisms; however there is an rRNA 16S homolog present in bacteria which corresponds to the 30S subunit of prokaryotic rybosome. Both 12S and 16S genes are widely used as highly conserved markers for phylogenetics studies, and are often used together to increase the resolution of identification. In recent years these genes have also been tested as a tool in epidemiology of vector-transmitted diseases to identify vector lineages and sources of blood meals from vector-blood samples. History The MT-RNR2 gene sequence was firs published in 1981 along with the rest of the Human Mitochondrial DNA (Anderson, et al. 1981). This gene is part of the first full sequence of the human mitochondria, know as the Cambridge Reference Sequence (CRS), and was the first attempt to start the human genome project. The group responsable for the publication of the CRS worked under Fred Sanger at the MRC Laboratory of Molecular Biology in Cambridge University. The gene was extracted and decoded using the Sanger Sequencing Method from cells from placental tissue. The MT-RNR2 has gone through two major revisions and resubmissions. The first resubmission was in 1999 (Andrew, et al. 1999) and second and final in 2009 as a direct submission to NCBI in 2009 by the National Center for Biotechnology Information. Annotation Primary Source: HGNC (HUGO Gene Nomenclature Committee) NCBI Gene ID: 4550, HGNC ID: 7471 NCBI Referenced Sequence: NC_012920.1 Location and gene family: Mitochondrial Chromosome, Ribosomal RNA genes http://www.ncbi.nlm.nih.gov/gene/4550 Target and use 16S-Like Genes for Phylogenetics and Barcoding 16S-like genes have been used as molecular markers since the 80s through both cloning and rapid comparison of short sequences methods among and within taxa (Sogin, Elwood and Gunderson, 1986a; Medlin, et al. 1988). Their value in phylogenetics derives from their conserved presence in almost all taxa, dating back to single-cell-organism's ribosomal coding genes. In Eukaryots, 16S is a mitochondrial, highly-mutational gene; a desierable characteristic not only for phylogenetic analysis but also for genetic barcoding . Barcoding differs from phylogenetics in that the taxa imput is unknown, and markers are used for taxa sorting. A desireable barcoding marker has traditionally been short enough so that it can be fully sequenced (although this is changing with next-generation sequencing), variable enough within species but conserved throughout evolution, and has to have non species-specific regions for primer design. Recent studies have validated 16S-barcoding equally eficient to COI-barcoding, which has traditionaly been used as the preferable mitochondrial marker for barcoding (Hamady, et al. 2008; Vences, et al. 2005). Alzheimer Disease Linked Gene Humanin (HN) is a 24-amino acid neuroprotective and antiapoptotic peptide believed to derive from a portion of the mitochondrial MT-RNR2 gene. HN was initially identified as a neuroprotective factor against Alzheimer's diseas-specific triggers (Bodzioch, et al. 2009). The exact location of the gene(s) encoding the peptide has not been determined conclusively; however, the 1567-base cDNA cotaining the open reading frame of HN is 99% identical with a fragment of MT-RNR2 (Hasimoto, et al. 2001). Landscape epidemiology The use of mitochondrial markers for the correct identification of vectors, parasites and blood-meal sources has become incresingly important as epidemiology has taken landscape and molecular approaches. For instance, the identification of feeding sources for Chagas disease vectors through barcoding with 12S clonal markers, or the use of varios mitochondrial loci to profile and correctly identify Aedes Mosqiuito biotypes, are among some of the uses epidemiologist are giving to mitochondrial markers (Cook, et al. 2005; Pizarro, et al. 2008). The validation of markers from 12S and 16S as an addition to the traditionally used COI mitochondrial gene, is allowing a higher ID resolution and increased feedback for species recolection, specially when targeting multiple, unkown sample-sources. References Marek Bodzioch, Katarzyna Lapicka-Bodzioch, Barbara Zapala, Wojciech Kamysz, Beata Kiec-Wilk, Aldona Dembinska-Kiec, Evidence for potential functionality of nuclearly-encoded humanin isoforms, Genomics, Volume 94, Issue 4, October 2009, Pages 247-256, ISSN 0888-7543, 10.1016/j.ygeno.2009.05.006. Anderson,S., Bankier,A.T., Barrell,B.G., de Bruijn,M.H., Coulson,A.R., Drouin,J., Eperon,I.C., Nierlich,D.P., Roe,B.A., Sanger,F., Schreier,P.H., Smith,A.J., Staden,R. and Young,I.G. Sequence and organization of the human mitochondrial genome. Nature 290 (5806), 457-465 (1981) Andrews,R.M., Kubacka,I., Chinnery,P.F., Lightowlers,R.N., Turnbull,D.M. and Howell,N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet. 23 (2), 147 (1999) M L Sogin, H J Elwood, and J H Gunderson.Evolutionary diversity of eukaryotic small-subunit rRNA genesPNAS 1986 83 (5) 1383-1387 Linda Medlin, Hille J. Elwood, Shawn Stickel, Mitchell L. Sogin. The characterization of enzymatically amplified eukaryotic 16S-like rRNA-coding regions. Gene, Volume 71, Issue 2, 30 November 1988, Pages 491–499 Hamady, M., Walker, J. J., Harris, J. K., Gold, N. J. & Knight, R. Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex. Nature Methods 5, 235–237 Miguel Vences, Meike Thomas, Ronald M Bonett and David R Vieites. Deciphering amphibian diversity through DNA barcoding: chances and challengesPhil. Trans. R. Soc. B October 29, 2005 360 1462 1859-1868; doi:10.1098/rstb.2005.17171471-2970 Y. Hashimoto, et al., A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta, Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 6336–6341 Cook S, Diallo M, Sall AA, Cooper A, Holmes EC (2005) Mitochondrial markers for molecular identification of Aedes mosquitoes (Diptera: Culicidae) involved in transmission of arboviral disease in West Africa. J Med Entomol 42: 19–28. Pizarro JC, Stevens L (2008) A New Method for Forensic DNA Analysis of the Blood Meal in Chagas Disease Vectors Demonstrated Using ''Triatoma infestans''from Chuquisaca, Bolivia. PLoS ONE 3(10): e3585. doi:10.1371/journal.pone.0003585